Encephalopathy is found in nearly all autopsy cases of AIDS whether associated with dementia or not. With emerging, life-prolonging therapy of AIDS infection of the immune system, be number of cases with overt dementia is likely to increase. It has been shown that it is, apparently, the endothelial cell which provides the portal of entry, if not the primary target of AIDS infection of the central nervous system (CNS). A permanently effective anti-viral therapy would require not only eradication of the virus in the immune system but also in the CNS. Most drugs fail to penetrate the endothelial blood-brain barrier. It therefore would appear useful if one had a vehicle that targets therapeutic agents specifically into the brain endothelial cell via receptor-mediated endocytosis. We have recently developed a monoclonal antibody (anti-EBA) reactive exclusively with an antigen specific to the blood-brain barrier. We now propose to examine whether liposomes covalently conjugated with anti-EBA, can be used as a vehicle to carry solutes, including anti-viral drugs, directly and specifically into brain endothelial cells. To explore the feasibility of this approach we will (1) produce conjugates of liposomes with varying amounts of anti-EBA by several conjugation procedures; (2) examine stability of the resulting conjugates (anti-EBA-L) in serum; (3) prepare anti-EBA-L of varying sizes; (4) examine receptor (epitope)-mediated endocytosis of anti-EBA-L in brain endothelial cells in vitro; (5) examine terminal complement complex-mediated endocytosis of anti-EBA-L in vitro; (6) examine release of endocytosed liposomal contents from lysozomes into the cytoplasm in vitro; (7) examine rate and specificity of brain endothelial uptake of anti-EBA-L after intravenous injection; (8) examine release of intravenously administered liposomal contents of anti-EBA-L from brain endothelial cell lysozomes into cytoplasm; (9) purify anti-EBA by immunoprecipitation and produce additional monoclonal antibodies to blood-brain barrier to be used in conjugation with existing anti-EBA to maximize rapidity of endocytic uptake; and (10) examine cooperativity for endocytosis of anti-EBA with other cell surface monoclonal antibodies on the same liposome.